A number of medicinal substances absorbed by the oral route must exert their effect only at the intestinal level and not before. Thus it is necessary that these substances remain for a given time in the stomach without these different agents acting on a level in the stomach so as to be completely digested.
Furthermore it is often desirable that the medicinal effect of an active substance be prolonged for a significant period of time in order to achieve a sustained-release effect.
For one or the other of these reasons or for both of these reasons together, it is very often necessary to protect the medicinal substance by a biodegradable and non-toxic covering, as a way to provide microencapsulation. Until now, resort has usually been made to microencapsulation techniques employing gelatine as a protecting agent.
It is known that gelatine is constituted by collagen, partially denatured and degraded by thermal, enzymatic, or chemical treatment. The treatments make the proteins vary fragile and the mean molecular mass of gelatine is lowered by rupture of the reticulated bonds and/or the peptide bonds. At best, the mean molecular mass is about 120,000; this lowering of the molecular mass considerably augments the solubility of the gelatine, especially in an aqueous medium, under the action of heat and acids. The gelatine does maintain a certain amount of the helicoidal structure, but this structure is more fragile than that of natural collagen. See A. Vers. Int. Rev. of Connective Tissue Research, Vol 3 (1965), 113-120. In effect the gelatinous material disappears even at temperatures less than 37.degree. C. The partial structure of the gelatine is rapidly destroyed in the organism and no longer protects against enzymatic action, especially against the enzymes in gastric juices.
In the course of a number of studies carried out on native collagen, the investors came up with the idea of exploiting certain properties of the product, in order to obtain new forms of microencapsulation for medicinal substances permitting a sustained release of the latter that is a good deal more sustained than the release obtained when gelatine is used for the microencapsulation.
The mean molecular mass of a native collagen is equal to or greater than 300,000 daltons. The collagen macromolecule which is wider than 15 angstrom units and longer than 2990 angstroms units is constituted by 3 peptide chains each having a molecular mass of 10,000 daltons. It is characterized by the presence of a glycine residue in every third amino acid residue the molecule as well as by a high content of hydroxy-proline. Between the chains there exists covalent chemical bonds which are bonded on at least one side to the end of the peptide chain, call telopeptides. This latter part is not present in a helical coil structure having a length of about 50 angstroms units. The three peptide chains are wound in a triple helix around a common axis. It can be determined that in this triple helix structure, the presence of the reticulated bonds and the size of the macromolecules are the essential factors for the partial insolubility of the collagen and for its resistance to enzymes. In effect the proteolytic enzymes (with the exception of collagenase) do not act on the collagen structures and will only digest the telopeptides, which are not in helicoidal form. This is evidence of the role of the helicoidal structure of the collagen as a protector from enzymatic action. See J. F. Woessner, J. B. Treatise on Collagen, 1968, vol. 2, pp 252-330. The temperature where the helicoidal structure disappears is 37.degree. C.